Systems and methods to deliver photodisruptive laser pulses into tissue layers of the anterior angle of the eye

ABSTRACT

The invention relates to systems and methods for accessing tissue layers of the anterior chamber angle of an eye, targeting one or multiple treatment zones within the anterior angle area of the eye and delivering focused photodisruptive laser pulses with pulse durations &lt;50 picoseconds creating channels into various anatomical structures within the anterior angle of the eye.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a division of application U.S. Ser. No. 13/442,854 filed on Apr.10, 2012. This application further claims the benefit of the U.S.provisional application No. 61/473,806, filed Apr. 10, 2011, the contentof which is considered incorporated by reference herein in its entirety.To the extent the following description is inconsistent with thedisclosure of the provisional application, the following descriptioncontrols.

BACKGROUND OF THE INVENTION

Lasers have been used for several decades in the treatment of glaucoma.The 2 most common laser treatments for primary open angle glaucoma(POAG) are ALT (Argon Laser Trabeculoplasty) and SLT (Selective LaserTrabeculoplasty). See for example U.S. Pat. Nos. 3,884,236; 8,066,696;5,549,596; 6,319,274. They work by applying laser pulses into theTrabecular Meshwork (in the anterior angle of the eye). These laserpulses are focused to around 50 micrometer diameter for ALT and around400 micrometer for SLT. Those laser spots are targeted to lay overSchlemm's canal and cause an increased outflow through the treatedTrabecular meshwork area. In both procedures at least 180 degrees of theeye angle is treated with typically 50 to 100 laser pulses (each pulseis applied to a new target zone-treatment area). The working mechanismfor ALT is blanching of the Trabecular meshwork that increases theoutflow by stretching the Trabecular Meshwork between the blanched(laser treated areas). The ALT laser with a typical setting of 600 mWand 0.1 s pulse duration (at 514 nm or 532 nm) causes a thermal tissueinteraction. In SLT treatment the laser causes cavitation bubbles in thetarget tissue due to its shorter pulse duration of about 3 nanosecondsand higher peak power (created by pulse energies of around 0.3 mJ to 1.6mJ).

Both procedures have a good success rate by increasing aqueous humoroutflow that creates a substantial drop in intraocular pressure ofaround 20%. Both procedures can be performed in minutes with a simpleslit lamp procedure in the office (no OR visit required). In bothprocedures, the eye does not need to be opened (non-invasive procedure),therefore the treatment risks and complication rates are minimal. Theproblem of these procedures as published in many studies is that it doesnot work effectively in all patients and in the successful cases theeffect wears off over the course of a few (1-3 years) and the IOP risesback to its baseline level. The procedure can be repeated once with ALTand 2-3 times with SLT, but after those repeats the tissue damage in theTrabecular meshwork that is created through those multiple proceduresultimately prevents any further IOP lowering effect.

A less frequently used laser procedure called ELT (Excimer LaserTrabeculostomy) uses an Excimer laser pulse (wavelength in the UV range)to actually drill holes into the Trabecular Meshwork. See for exampleU.S patent applications: 20080082078; 20040082939. Because completeopenings are created to Schlemm's canal (unlike ALT and SLT), the IOPlowering effect is similar or better than ALT/SLT and in the same timeonly a few open holes need to be drilled with ELT versus 50-100treatment zones in a typical ALT/SLT procedure. Some studies furthersuggest that the ELT effect is longer lasting then ALT/SLT due to someobserved long term patency of those holes. Furthermore ELT might berepeated more often since a smaller area of the Trabecular Meshwork istreated each time. The downside of ELT is the fact that UV wavelengthlight does not penetrate the cornea and aqueous humor, therefore thelaser can only be applied to the Trabecular Meshwork in an operatingroom procedure, where the eye is opened and a fiber probe is insertedinto the anterior chamber all the way up to the Trabecular Meshwork.

In recent years the effectiveness of having one or multiple holes in theTrabecular Meshwork (connecting to Schlemm's canal) has also beendemonstrated with several implants, placed through the TrabecularMeshwork that create an opening into Schlemm's canal. See for exampleU.S patent applications: 20120071809, 20070276316. Those are howeveralso invasive (full operating room) procedures using an implant.

Another approach to drain aqueous humor out of the anterior chamber hasbeen successfully demonstrated by implanting a drainage tube through thescleral spur region and into the suprachoroidal space. See for exampleU.S patent application: 20110098629. This is however also an invasive(full operating room) procedures using an implant.

Most recently, there have been animal tissue studies applying ultrashortphotodisruptive laser pulses to the trabecular meshwork with limitedsuccess. Hiroshi Nakamura et. al. Investigative Ophthalmology & VisualScience, March 2009, Vol. 50, No. 3. Performed an ex vivo study onprimates delivering photodisruptive laser pulses into the anterior angleof the eye. He presents several limitations and challenges in the paperconcerning the goal of creating a hole through the Trabecular Meshwork.These limitations and challenges have so far prevented a successful useof such a non-invasive laser procedure in the angle of the eye.

The inventions described herein relate to a new devices and methods toovercome those limitations and challenges and therefore allow thecreation of holes and channels in the Trabecular Meshwork and otherplaces in the angle of the eye in a non-invasive procedure that can berepeated as many times as necessary.

Other examples of related prior art are U.S. Pat. Nos. 8,056,564;4,391,275; 5,288,288; 7,912,100

BRIEF SUMMARY OF THE INVENTION

Photodisruptive laser pulses in the range of <1000 femtoseconds havebeen successfully applied to make incisions into various tissues of theeye. The main focus to date has been using a femto second laser forvarious cornea incisions such as LASIK flaps, intrastromal incisions,Limbal Relaxing Incisions, Keratoplasties and cornea entry incisions. Inmore recent years femtosecond lasers have also been successfully appliedto the capsule and the lens of the human eye in femtosecond laserassisted cataract procedures.

The main benefit of these photodisruptive laser pulses lays in the factthat the eye tissues, that are treated transmit the wavelengths of thetypically chosen lasers, usually in the near infrared or visible rangeand therefore allow the laser to be focused through the cornea, aqueoushumor, lens capsule and lens without much scattering or absorption. Thelaser pulses are always focused to a very small spot size in the rangeof a few micrometers, where a laser induced optical breakdown isachieved in any tissue or liquid (e.g. aqueous humor) that falls withinthe spot size location.

This optical breakdown (photodisruptive breakdown) creates a microplasma followed by a small cavitation bubble, which can be used to cutand dissect tissue areas of any size and shapes by scanning a sequenceof many such laser pulses over a desired volume in the eye.

Since the tissue layers in the laser path above and below the focuspoint are below the optical breakdown threshold and since they mostlythe laser wavelength, they remain unaffected by the laser beam. Thisprinciple allows non-invasive photo disruptive eye surgery since noincision from the outside needs to be made.

There is a threshold of a minimum laser fluence (laser peak powerdivided by focus area) required to achieve the optical breakdown. Thelaser peak power goes up no with higher pulse energy (typically in theμJ range) and shorter pulse duration (typically <600 fs). The laserfluence for any given peak power goes up as the focus area goes down.Achieving a small spot size is therefore critical in achieving a highfluence that exceeds the optical breakdown threshold.

The way of achieving a high enough fluence for breakdown by increasingthe us laser pulse energy is less desirable since a higher pulse energycomes with a larger cavitation bubble and associated shock wave. Thelarger the cavitation bubble the less precision is achieved in cuttingany features with a sequence of pulses. Furthermore a large shock waveis considered a undesired side effect since it has the potential todamage surrounding tissues.

Priority is therefore given to minimizing the spot size to achieve anabove threshold laser fluence while using laser pulses within a lowpulse energy range of <50 μJ per laser pulse.

These principles have been successfully implemented in femto second eyelaser systems treating the cornea or capsule/lens of an eye. The laserdelivery systems can achieve good focusing access to the cornea and lensthrough large focusing lens assemblies positioned within a few cm abovethe eye. Typical laser beam focusing convergence angles achieved arenumerical apertures of NA>0.15 (full angle Θ>15 deg) and in someoptimized cases NA>0.3.

According to: Formula 1

$\Theta = {M^{2}\frac{360\lambda}{\pi^{2}\omega_{0}}}$

Θ=full focusing convergence angle in degrees

λ=laser wavelength

ω=laser beam focus radius defined by 1/e² cut off

M²=beam quality factor determined by the total aberrations

If beam aberrations can be kept to a minimum e.g. M²<1.3 (M²=1 is thetheoretical minimum with no aberration at all) then the above focusingangles of NA>0.15 (Θ>15 deg) and NA>0.30 (Θ>30 deg) the resulting spotsize diameters (2 ω₀) will be <8 μm and <4 μm respectively (for a laserwavelength λ=1 μm).

The minimization of aberrations is critical in achieving such small spotsizes.

The tissue layers in the cornea and lens/capsule are relatively easyaccessible for any laser beam from the outside.

Due to the fact that the existing systems focused laser beams enter theeye in a straight vertical line that is perpendicular to the centralarea of the cornea (and top surface of any used patient interface) theaberrations can be kept small enough to allow small spot sizes. Suchfemtosecond cornea and lens/capsule systems typically reach beam qualityfactors of M²<2.

The same easy access is not available for reaching the anterior camberangle tissue layers of the eye with a highly focused laser beam.

Furthermore the tissue layers in the anterior angle of the eye containblood vessels that will start bleeding when hit or cut by photodisruptive laser pulses.

Therefore, there are several limitations and considerations that need tobe overcome in order to deliver photo disruptive laser pulses to theanterior angle of the eye. Very limited success has been demonstrated sofar in reaching these tissue layers (e.g. Trabecular Meshwork or scleralspur) with the goal of applying a laser pulse sequence that can create adrainage channel (hole) into and through those tissue layers.

Accessibility consideration factors for a highly convergent focusedlaser beam targeting the tissue layers of the anterior chamber angle:

Eye Anatomy:

The eye anatomy see FIG. 9 restricts the angular accessibility of theanterior angle (e.g. Trabecular Meshwork 3104) particularly in thevertical plane (defined here as a plane that includes the z-axis goingcentrally).

FIG. 3 shows a histology picture of the anterior angle in such avertical cut. This eye shows a rather narrow angle of only 20 degrees.Typical angles in human eyes (including Primary Open AngleGlaucoma—POAG) are between 30 and 50 Degrees.

This vertical plane (vertical angle axis) represents the most restrictedaxis in terms of angular accessibility since the tangential access plane(the plane that includes the rim of the TrabecularMeshwork—perpendicular to the vertical plane) has a somewhat largeraccessibility angle.

There are further factors limiting angular access to the eye (particularthe already critical vertical plane).

Eye Geometry Variations:

The anterior angle accessibility varies widely from eye to eye. Forexample in highly myopic eyes the angle can be larger than 45 Degrees,while it becomes more narrow in Hyperopic eyes. FIG. 4 shows a moreaverage 40 degree angle opening 3015.

Other Factors and Limitations of Anterior Angle Angular Access:

Total Internal Reflection, Gonioscopy Lens Requirement:

Due to the geometry of the cornea and anterior angle the light rays outof the anterior angle cannot exit the cornea due to total internalreflection. An optical interface with a similar index of refraction istherefore required on top of the cornea. This is called a gonioscopylens (from here on referred to as a gonio lens). This invention includesseveral new gonio lens variations and designs that address and solvebesides other features the wide angle laser delivery issues andlimitations. FIG. 5 and FIG. 6 illustrate these principals.

Beam Aberrations:

The focusing laser beam has to go through several interfaces such asgonio lens, goniogel, cornea and aqueous humor. There are numerous casesof beam aberrations limiting the focusing power due to:

The wavefront of the beam hits many of those interfaces at high angleswhich is prone to cause astigmatism and higher order aberrations.

The interfaces curvatures such as the cornea vary from eye to eye andare not aberration free, especially at shallow incidence angles. Themost upper vertical beam limit line runs at some point almost parallelto the cornea and endothelial cell layer. This causes significantaberrations in that part of the focusing laser beam. See for exampleFIG. 10.

The sagittal and tangential (vertical and horizontal) planes are exposedto significant different aberrations due to different interfacecurvatures in their respective planes.

The sagittal and tangential planes have different focusing requirementsas discussed above (see FIG. 7) and therefore also experience differentlevels of aberrations.

All these factors need to be considered in the design and the methods ofa delivery system, that can meet the small focusing requirements at theanterior angle. This invention addresses those limitations.

The limitations that need to be addressed and overcome can be summarizedinto the following categories:

The anatomical limitations of the human eye, in particular therelatively narrow access angle to the Trabecular Meshwork between theiris and the cornea are limiting the maximal possible focusing angle inthat dimension. Furthermore human eyes show a great range of variabilityin this anatomical angle. In particular the last 1-2 mm before theactual chamber angle has great access variability between 0 deg (in caseof a closed angle) to 50 deg opening based on the exact iris position.

Often the last 1 mm distance approaching the anterior angle from thecenter of the anterior chamber is hard to visualize even with a goniolens a and can close off very rapidly due to iris synechia and irisbulging.

The laser beam cannot enter the eye perpendicular, but rather enters thecornea under a shallow and at some outer beam limits at an almostparallel angle. This dramatically increases the amount of aberrationsthat the laser beam wave front experiences during the beam propagationinto the eye. Furthermore any contact interface and gonio lens thatapplies pressure to the cornea will induced aberrations such as corneawrinkles that need to be overcome and/or compensated for.

The target region contains tissues of varying absorption and opticalbreakdown threshold characteristics since there is a great patientvariability in pigmentation and presence of blood vessels or blooditself. These variations create large variability in the photodisruptive breakdown threshold fluency of the laser-tissue interactionsand need to be considered and compensated for.

Due to total internal reflection, the angle is not directly accessiblewithout the use of a gonio lens. A specific gonio lens design isrequired to minimize aberrations, allow for sufficient eye fixation andmost importantly to allow transmission of a highly convergent laser beamas described above.

To allow integration of a gonio lens into a laser delivery system apatient interface with specific features is required.

The present inventions provides a method for overcoming the limitationsdescribed above. In particular the invention provides the followingmethod:

A third method for delivering a particular pulse sequence of circular orelliptical spot size femtosecond laser pulses to create a hole(s) orchannel(s) into the tissue layers of the anterior angle of an eye. Themethod describes a scanning pattern that can for example be appliedduring the laser firing in the first method step e. or the second methodstep f. to create the hole and channel into the desired target tissuelayers. Method to target the treatment zone(s) using one or multiplelasers.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a laser focus with a 3 μm diameter and a 20 degconvergence angle

FIG. 2 illustrates a laser focus with a 3 μm diameter and a 40 degconvergence angle

FIG. 3 illustrates a 20 deg laser focus into the anterior angle regionof an eye

FIG. 4 illustrates a 40 deg laser focus into the anterior angle regionof an eye

FIG. 5 shows the concept of total internal reflection

FIG. 6 illustrates a laser beam path using a direct gonio lens

FIG. 7 shows a simulated laser beam with different focusingcharacteristics in the horizontal and vertical axis

FIG. 8 illustrates a laser focus being scanned back and forward across atissue interface

FIG. 9 shows the anatomical features of the anterior angle of an eye

FIG. 10 illustrates a large photocoagulation zone due to a defocusedlaser beam

FIG. 11 shows a aiming beam and treatment laser beam focusing into theangle

FIG. 12 illustrates an alignment motion for an aiming laser beam

FIG. 13 shows a circular laser firing pattern in the anterior angletissue layers

FIG. 14 shows a corkscrew laser firing pattern in the anterior angletissue layers

FIG. 15 shows a elliptical photocoagulation zone in the angle of an eye

FIG. 16 shows a detailed delivery system design

FIG. 17 illustrates a detailed patient interface design

FIG. 18 shows a detailed laser shaping optical delivery system componentdesign

FIG. 19 shows a detailed laser shaping optical delivery system componentdesign

FIG. 20 shows a detailed laser shaping optical delivery system componentdesign

FIG. 21 shows a detailed laser shaping optical delivery system componentdesign

FIG. 22 illustrates a full system block diagram

FIG. 23 illustrates a laser firing pattern

FIG. 24 illustrates a laser firing pattern

FIG. 25 illustrates the laser beam path of a specific mirror gonio lens

DETAILED DESCRIPTION OF THE INVENTION

The word “fs-laser” throughout this disclosure stands for femtosecondlaser and is meant to cover any laser source, that can provide pulsedurations smaller than <50000 femtoseconds (50 pico seconds) with apreferable range of 10 fs to 500 fs. The word femtosecond can also beinterchanged with the word photodisruptive throughout the entiredisclosure. This ultra-short pulse requirement together with a smallspot size area (preferably <20 μm for circular focus and preferably <400μm² for elliptical focus) allows the use of very small pulse energies inthe range of <200 micro Joules (preferable range <50 micro joules) whilestill achieving a photodisruptive (plasma induced optical breakdown)tissue reaction that allows for the creation of a hole (tunnel) intissue layers in the anterior angle of the eye (e.g the TrabecularMeshwork). FIG. 9 shows the anatomical features of the anterior anglearea of the eye. It is critical to keep the pulse energies small sincethe undesired side effects such as shockwaves and large cavitationbubbles scale with the pulse energy, reduce precision and causeincreasing collateral tissue damage around the desired target zone.

FIG. 1. The small focus requirement leads to a large focusing beamconvergence angle (high numerical aperture NA) in the range of 10-90degrees. A 3 μm spot size diameter of a λ=1060 nm fs-laser beam with anaberration free beam quality factor of M²=1 requires about 20 degrees(1/ê2) of full convergence (often referred to as beam divergence) angleas can be seen in the simulated coherent laser beam 3003 horizontal and3006 vertical propagation calculation of FIG. 1.

Because of significant wave front distortions of the laser beam, as itpropagates through various optical and eye anatomical interfaces thecoherence quality of the wave front is reduced resulting in a largerspot size. To maintain the same small spot size in the example above thefull convergence angle to reach a 3 μm spot size diameter goes up toabout 36 degrees (for an M̂2 of 1.8) as shown in the simulation in FIG.2.

Furthermore these theoretical values are defined as a 1/ê2 beam cut offvalue. If the beam had only exactly that room to propagate and anythingoutside this envelope would be cut off, then that would result in alarger focus and lost pulse energy due to clipping.

To prevent this additional aberration and energy loss it is important toallow another 5-10 degrees of accessible angle to prevent excessiveclipping and to allow for some misalignment margin.

The present invention provides a method for overcoming the limitationsdescribed above. In particular the invention provides the followingthird method (as named in the parent application):

A first method (reference only) to optimize the fs-laser beam parametersto reach, target and create holes into the tissue layers of the anteriorangle of the eye: This will address the highly variable (eye to eye andsetup to setup related) beam aberration variations and geometrical anglesize variations of the anterior angle from eye to eye. This method isdescribed in the following steps from a. to f.

-   -   a. (Optional) When a laser delivery system with an adjustable        beam convergency angle is used, pre-measured patient data of the        anterior angle access angle e.g. through OCT (optical coherence        tomography) before treatment is used to course adjust the        vertical beam axis convergence angle (and horizontal axis in        same way for circular focus version) to roughly match the        accessible angle.    -   b. Use a delivery system with a fixed beam full convergence        angle of 30 to 60 deg if circular or 30-60 deg in the vertical        axis and 40-90 degrees in the horizontal axis if elliptical. The        preferred full convergence angles are 40 deg (+/−5 deg) in both        axis if a circular beam is delivered and 40 deg (+/−5 deg) in        the vertical axis and 70 deg (+/−10 deg) in the horizontal axis        if a delivery system is used that allows elliptical focusing.        For most eyes with open angles these preferred settings will        achieve a spot size at the anterior angle tissue layers that is        close to a practical minimum. For eyes with partially closed        angles <45 deg in the vertical access angle, the preferred        settings will overfill the accessibility angle and this will        result in some partial laser beam clipping in the vertical axis.        The laser focus is then targeted into the desired tissue layer        surface in the anterior angle of the eye and once the laser        focus targeting has been completed the laser starts firing at a        low pulse energy preferably <10 μJ. These probing laser pulses        below the plasma breakdown threshold are then successively        increased in pulse energy until first optical breakdown        cavitation bubbles are detected (preferably by a vision system).    -   c. (optional) see FIG. 8. The focusing lens and therefore the        laser focus is scanned back 3031 and forward 3030 (preferably        +/−<750 μm in z-axis 3029 while pulse energy is being increased        in the sequence under b. to: assure the detected threshold        happened on the surface of the targeted anterior angle tissue        (e.g. Trabecular Meshwork) or closely below and not in the        aqueous humor and to: calibrate the actual z-distance of a laser        delivery system reference point (e.g. upper patient interface        plane) to the surface of the targeted tissue layer in the        anterior angle (e.g. trabecular meshwork surface).    -   d. (optional) Once the threshold has been determined as        described in step b. (and optional the z-calibration in step c.)        the same laser beam is preferably automatically defocused by a        predetermined amount using a z-scan of the focusing lens or        other lens in the delivery system. The preferred defocusing        adjustment moves the laser focus 0.7 mm (+−0.5 mm) deeper into        the target tissue (towards or into the sclera). This results in        an enlargement of the laser beam diameter on the target tissue        (surface of the anterior angle tissue layer) to about 500 μm        FIG. 10, 3201 for a laser beam with a circular convergence angle        of 40 deg 3203. After this defocusing adjustment 3202, resulting        in a focus position in 3200, the pulse energy is automatically        adjusted higher. This pulse energy is adjusted to a level such        that the resulting average laser power        P_(average power)=E_(laser pulse energy)R_(laser repetition rate)        times the applied laser on duration time during this defocused        sequence provides an amount of total energy        E_(total)=P_(average power)t_(laser on duration) that photo        coagulates the tissue area within the defocused diameter. For a        preferred laser repetition rate >100 kHz and a preferred        circular area of a 500 μm diameter beam and a preferred laser on        duration of <1 s the preferred laser pulse energy is >10 μJ.        Lower available pulse energy can be compensated by increasing        the laser on duration to achieve the desired amount of        photocoagulation. The laser beam area for this defocused large        beam (e.g. 500 μm circular diameter) is typically >1000 times        larger than typical achieved laser focus on the same surface        without defocusing (e.g. 10 μm circular diameter). Therefore any        conceivable rise in pulse energy (even to e.g. as high as >500        μJ) would still be far below the plasma threshold energy on this        large area. Furthermore the new laser focus 0.7 mm below the        anterior angle tissue layer surface is, because of significant        photon scattering and absorption of the tissue layers between        the surface layer and the 0.7 mm deep layer no longer reaching        the fluency level required to exceed the plasma breakdown        threshold. All laser power is therefore now absorbed and        scattered creating a thermal effect in and around the defocused        beam zone leading to photocoagulation versus a photodisruptive        cutting effect. The penetration depth of the coagulated tissue        volume depends beside the total delivered laser energy also on        the laser wavelength. The achieved coagulation zone (volume)        reduces or prevents any bleeding from the high fluency (above        threshold) laser pulses that follow this step (see step e.) and        create a hole or channel into the tissue layers. For a typical        photodisruptive (ultra short pulsed) laser wavelength around        1050 nm (+−50 nm) the absorption length is longer than for        shorter wavelengths such as used for example in a 532 nm        coagulation laser (similar to SLT and ALT). Such a shorter        wavelength, quasi cw (continuous wave) laser with a preferred        wavelength of 532 nm or 577 nm or 810 nm can be used as a second        laser source instead of the defocused photodisruptive main        laser. In that configuration the second source shorter        wavelength laser does not need to be focused in a highly        converging beam since it only needs to reach a preferred spot        size diameter of 500 μm (+−300 μm). Furthermore, if another        laser is used for the photocoagulation part, than that part of        the procedure can be performed before the non-invasive        photodisruptive laser procedure. For example the coagulation of        one or multiple treatment zones can be performed minutes or days        before the channel creating procedure on a laser slit lamp        setup. All the above parameter considerations for a preferred        circular laser beam are also applicable to a preferred        elliptical laser beam.    -   e. Once the threshold pulse energy is known from step b. and        optional z-calibration from step c. and the optional        photocoagulation (step d.) is completed, the laser will        preferably automatically adjust the treatment pulse energy in a        preset way relative to the threshold energy (preferably 3× to        10× the threshold energy) and preferably automatically fire a        preset scanning pattern to create one or multiple holes into the        desired target zone layers (e.g. through the Trabecular Meshwork        or into the suprachoroidal space) within the coagulated zone, if        created.    -   f. (optional) All steps b. to e. are preferably done in a fully        automated sequence immediately following each other and        parameters are optimized such that the entire laser procedure        time is preferably less than 10 s.

A second method (reference only) to measure and maximize the verticalangular laser beam access and therefore achieving minimal spot size atthe anterior angle tissue layers of an eye. The horizontal convergenceangle of the treatment laser beam is fixed to preferably 60 deg (+/−20deg) to create a small spot size in the horizontal axis in the range of<10 μm diameter depending on the overall aberrations.

Step a. The angular opening in the vertical axis is determined with thesame femtosecond laser delivery system just prior to firing thephotodisruptive femtosecond laser pulses by using a shape adjustablevisible aiming laser beam under live observation. FIG. 11 shows anaiming laser beam 3204 being focused collinear to the plannedphotodisruptive treatment beam 3206 into the target tissue layer of theanterior angle of the eye. In one embodiment, this is done by changingthe vertical aiming beam divergence from big to small until no light isclipping on the iris and cornea (both sides of the angle) or doing itreverse (small to big) until light starts to scatter on the outsidesurfaces of the angle. FIG. 11 shows the lower aiming beam envelopeclipping on the iris 3205. This scattered light feedback can be observedlive by the surgeon/operator or by an automated video/sensor analysissystem. While the beam cone is maximized, in the same time the deliverysystem is preferably constantly adjusted for centration in the angle ofthe eye to center the focusing beam cone in the angle to achieve thesetting of a maximum allowable vertical angle. This adjustment isillustrated in FIG. 12 The beam 3210 is moved in the directions 3211.

Step b. Once the maximum vertical accessibility angle to the targetregion has been determined the aiming beam is scanned back and forwardin the z-axis (above and below the target tissue plane) using a deliverysystem moving lens (e.g. the main focusing lens) until the visible beamdiameter on the target tissue layer is minimized. This minimum spotvisualization can be performed live by observation of the surgeonthrough a microscope or preferably by an automated vision system. Thenow known z-position of the delivery system optics is now used tocalibrate the z-distance of a delivery system reference point to theaiming beam focus position on the surface of the target tissue layer.

Step c. (optional) If the delivery system allows the adjustment of thevertical beam convergence angle for the photodisruptive treatment beam,then the vertical angle is now adjusted to match the maximum determinedaiming beam angle from step a. This sets the treatment beam up toachieve a minimum possible vertical spot size on the target tissuelayer.

Step d. (optional) Perform a coagulation step identical to the firstmethod step d.

Step e. The control system of the laser system now calculates and thensets the optimal photodisruptive laser pulse energy based on the inputfrom step a., b. and c. before the treatment laser is fired. The factorsfor this calculation are as follows: If the vertical treatment beamangle is adjustable then it has been set to the maximum vertical anglein step a. Since the horizontal focusing angle is fixed, the horizontalspot size axis is fixed as well ω_(0 horizontal fixed). The verticalspot size ω_(0 vertical) and therefore the spot size area A is accordingto formula 1 inverse proportional to the maximum vertical angle Θ.

${A_{{spot}\mspace{14mu} {size}\mspace{14mu} {area}} \sim {\omega_{0\mspace{14mu} {horizontal}\mspace{14mu} {fixed}}\omega_{0\mspace{14mu} {vertical}}}} = {\omega_{0\mspace{14mu} {horizontal}\mspace{14mu} {fixed}}M_{vertical}^{2}\frac{360\lambda}{\pi^{2}\Theta_{vertical}}}$

with

$\omega_{0\mspace{14mu} {horizontal}\mspace{14mu} {fixed}} = {M_{horizontal}^{2}\frac{360\lambda}{\pi^{2}\Theta_{horizontal}}}$

the spot size area A becomes: Formula 2

$A_{{spot}\mspace{14mu} {size}\mspace{14mu} {area}} \sim {M_{horizontal}^{2}\frac{360\lambda}{\pi^{2}\Theta_{horizontal}}M_{vertical}^{2}\frac{360\lambda}{\pi^{2}\Theta_{vertical}}}$

The required treatment pulse energy is: Formula 3

E_(pulse energy setting)=c E_(threshold pulse energy)

with E_(threshold pulse energy) being the minimum pulse energy requiredto achieve a photodisruptive optical breakdown on the desired tissuelayer and c being a factor by which the set pulse energy needs to exceedthe threshold pulse energy to achieve an efficient photodisruptivetissue effect for cutting and drilling a hole into the tissue layers.The preferred setting for c is 3 to 10. The threshold for thephotodisruptive optical breakdown depends on the laser fluency F, being:Formula 4

$F_{threshold} = \frac{E_{{threshold}\mspace{14mu} {pulse}\mspace{14mu} {energy}}}{t_{{pulse}\mspace{14mu} {duration}}A_{{spot}\mspace{14mu} {size}\mspace{14mu} {area}}}$

Therefore:E_(threshold pulse energy)=F_(threshold)t_(pulse duration)A_(spot size area)or: Formula 5

E_(threshold pulse energy)˜A_(spot size area)

Combining formula 2, 3 and 5 leads to: Formula 6

$E_{{pulse}\mspace{14mu} {energy}\mspace{14mu} {setting}} \sim {{cM}_{horizontal}^{2}\frac{360\lambda}{\pi^{2}\Theta_{horizontal}}M_{vertical}^{2}\frac{360\lambda}{\pi^{2}\Theta_{vertical}}}$

If the vertical angle is not adjustable, then it has been set to a fixedpreferred angle of Θ_(vertical)=40 deg (+/−15 deg). Depending on themeasured maximum vertical accessibility angle in step a. this fixedvertical angle Θ_(vertical) is either smaller or larger than the maximumaccessible angle. If it is larger than the maximum accessible angle thena clipping factor f_(clip) needs to be considered that reduces the laserpower on target an enlarges the spot size in the vertical axis.Including this clipping factor the laser control system calculates therequired pulse energy setting for the following laser treatmentaccording to Formula 7:

$E_{{pulse}\mspace{14mu} {energy}\mspace{14mu} {setting}} \sim {f_{clip}c\; M_{horizontal}^{2}\frac{360\lambda}{\pi^{2}\Theta_{horizontal}}M_{vertical}^{2}\frac{360\lambda}{\pi^{2}\Theta_{vertical}}}$

The beam quality factors M_(horizontal) ² and M_(vertical) ² depend onthe sum of all aberrations of the laser system including the deliverysystem optics, patient interface, patient contact lens (goniolens) theinterface to the eye and to some extend the condition of the cornea andanterior chamber of the eye. Most of these beam quality factors aresystem specific and are preferably calculated and measured. A high levelof accuracy in determining those quality factors is achieved byperforming photodisruptive laser threshold measurements using model andcadaver eyes on the final laser system setup. The f_(clip) loss factoris also determined by performing photodisruptive laser thresholdmeasurements using model and cadaver eyes on the final laser systemsetup. They are performed for a range (15 deg to 50 deg) ofaccessibility angles (step a.) and saved as a table within the lasercontrol system. Once the laser procedure has started and the actualvertical accessibility angle has been determined in step a, the controlsystem looks up the corresponding f_(clip) loss factor and calculatesthe final laser pulse energy setting E_(pulse energy setting) accordingto formula 7.

Step f. After the control system sets the treatment laser pulse energy,the laser will preferably automatically fire a preset scanning patternwith reference to the laser beam alignment in step a. and thez-calibration in step b. to create one or multiple holes into thedesired target zone layers (e.g. through the Trabecular Meshwork or intothe suprachoroidal space) within the coagulated zone, if created.

Step g. (optional) All steps a. to f. are preferably done in a fullyautomated sequence immediately following each other and parameters areoptimized that the entire laser procedure time is preferably less than10 s.

A third method for delivering a particular pulse sequence of circular orelliptical spot size femtosecond laser pulses to create a hole(s) orchannel(s) into the tissue layers of the anterior angle of an eye. Themethod describes a scanning pattern that can for example be appliedduring the laser firing in the first method step e. or the second methodstep f. to create the hole and channel into the desired target tissuelayers. The method is as follows:

Step a. The beam (round or elliptical focus) will be scanned in acircular pattern to create the hole and channel into the desire targettissue layers. The preferred starting cutting circle diameter is 250μm+/−100 μm. The preferred spot separation is 10 μm+/−7 μm. The firstcircle is cut at a z-alignment that brings the focus plane of thetreatment laser beam within +/−10 μm of the surface plane of the targettissue layer.

Step b. Several additional circles (preferably 10+/−7 more) are beingcut successively moving deeper into the tissue layers. Each new circleis preferably focused 7 μm+/−5 μm deeper than the last see FIG. 13 orthe circles are continuously going deeper into the tissue in a corkscrewtype of scanning pattern, see FIG. 14 with the same slope (7 μm deeperper revolution).

Step c. (optional) The laser focus plane is moved back up to theoriginal surface of the top tissue layer and the laser is now scannedover the entire circle area in a raster or spiral pattern with apreferred spot separation of 5 μm+/−3 μm. Similar to step b the focusplane is then lowered by 7 μm+/−5 μm and the same areal cutting isrepeated. This is also repeated preferably 10 times.

Step d. The focus plane is moved back up to the original surface planeof the top tissue layer and the laser is now repeats the scan patternfrom step but with a preferably 30 μm+/−20 μm reduced diameter. Thismeans for the preferred case a new concentric circle diameter of 220 μm.Furthermore the amount of cutting circles or corkscrew rotations is nowincreased by preferably another 10 to a total of 20 circles. Thisresults in a preferred cutting cylinder depth of 20×7 μm=140 μm.

Step e. (optional) repeat step c. with a reduced diameter and extendeddepth according to step d.

Step f. Repeat step d. and step c. while further reducing the diameterand extending the cutting depth until the desired hole or channel depthhas been achieved. FIG. 24 shows an example of the total scanningpattern after 3 cycles with different diameters 3709, 3708, 3707 anddepths have been completed. The preferred cutting channel depth for theTrabecular Meshwork are in the range of 100 μm to 300 μm while thepreferred channel length for an access channel into the suprachoroidalspace is between 400 μm and 3 mm. Other desired target areas will haveother preferred channel lengths.

Step g. (optional) The laser pulse energy is increased (preferably by afactor of 2+/−0.8) and the laser is fired preferably 10 times back andforward along the central z-axis of the holes/channel with a scanningdepth amount that is equal to the hole/channel length. FIG. 23 shows theoverlapping linear micro destruction zones 3700 to 3706 of theindividual laser pulses after the first z-scan. 3300 represents the toptissue layer in the anterior chamber angle region. This step clears anyremaining tissue debris out of the channel. This step can be repeated afew times with a few seconds of pause in between to allow the cavitationbubbles to disappear.

Step h. (optional) The cutting sequence described in step a to step gcreates a slight cone shaped channel getting smaller diameter as thechannel progresses deeper into the tissue layers. This scanning sequenceand cone angle can be reversed by starting with the smallest circlediameter and going outwards while going deeper.

Step i. (optional) The channel can also be cut with a cross sectionalshape of an ellipse. Instead of circles the laser is scanned inelliptical shapes. For example an ellipse with the long axis beingvertical has the advantage of easier assuring a channel connection toSchlemm's canal since it runs somewhere behind the Trabecular Meshworkalong the horizontal plane see FIG. 15.

Step j (optional) In step a. instead of placing the first circle z-depthat +/−10 μm within the top surface layer of the tissue, the firstcutting plane is adjusted 20 μm below the tissue surface. This thintissue layer can still be sufficiently penetrated by the laser energyand the resulting cavitation bubble below the surface explodes the abovetissue layers away more effectively. This method variation requires apreferably 2 times larger laser pulse energy setting and is thereforenot available for certain low cost, low power laser systems.

Step j. (optional) To create multiple holes and channels step a. to stepi. are repeated at a different locations.

Step k. (optional) (named as fourth method in parent application) As avariation, using a low cost laser delivery system that only contains az-axis scan ability, the channel can be cut by only performing step g,see FIG. 23. The amount of back and forward scanning cycles is nowincreased to preferably 50 times+/−30 times.

Although the present invention has been described in considerable detailwith reference to the preferred versions thereof, other versions arepossible.

The scope of this patent and the appended claims is limited to a “thirdmethod” as described above. The first and second methods from the parentapplication are included since they are referenced in the third method.

1. A third method of delivering photodisruptive laser pulses into targeted tissue layers of the anterior angle of the eye using a sequence of cutting circles that progress from large to small and with varying z-depths, selected spot separation, layer separation and position relative to the target zone that create a channel opening through the targeted tissue layers.
 2. A method of claim 1 where the areas within the cutting circles are treated with photodisruptive laser pulses following a repetitive sequence.
 3. A method of claim 1 where the cutting circles are elliptical.
 4. A method of claim 1 where the channel cutting procedure is ended by a sequence of laser pulses that are scanned back and forward along the central z-axis of the treatment zone.
 5. A method of claim 1 where the first cutting circle is placed below the surface of the target tissue area.
 6. A method of claim 1 where the cutting circles change from small to large during the progression of the cutting sequence.
 7. A method of claim 1 where the laser pulse sequence is repeated multiple times at different target locations to create multiple channel openings.
 8. A method of claim 1 where the diameter of all cutting circles is 0 and therefore every circle effectively becomes a spot. 